Isolation of HIV from saliva is a rare event, and the oral cavity does not appear to be a route for viral transmission. We have described a salivary factor that agglutinates HIV, forming large complexes. We have recently identified a second salivary activity that decreases HIV infectivity in the absence of filtration. Our hypothesis is that the salivary factors act as a natural host-defense mechanism to clear virus in infected individuals, and as a barrier to infection in uninfected individuals. The salivary factors help to remove HIV form oral secretions and virus is therefore not available for transmission or infection via the oral route. In this application we propose to further characterize the nature of the agglutinating and "prefiltration" salivary HIV inhibitors, to study their mechanism of action, and to correlate the presence of cell free and cell associated HIV with levels of inhibitory activity in saliva obtained from HIV seropositive individuals. Once the salivary HIV inhibitors are identified, the mechanism of action in vitro, and the possible in vivo significance will be assessed. It is clear from our studies that there is a selective interaction between a salivary factor and HIV, but the importance of this reaction remains to be demonstrated. The possible role of salivary anti-HIV factors in vivo will be studied by correlating activity with the presence of HIV in seropositive individuals, and also with the stage of the disease. If a specific anti-HIV factor is purified from saliva, one will have opened up a potential new avenue for therapeutic drug design based upon a naturally produced anti-viral substance.